Delta
opioid delta receptor (DOP) agonists were expected to be
analgesics and many researchers tried to develop the
SNC80 derivatives. However, the derivatives were dropped at the stage of early clinical trials because of undesirable side effects and weak
analgesia. On the other hand, DOP agonists have been proposed as attractive candidates for the novel
psychotropic drugs. We recently succeeded in synthesizing a novel selective DOP agonist
KNT-127.
KNT-127 produced neither
catalepsy nor convulsive effects. We have demonstrated that
KNT-127 has potent
anxiolytic-like effect in rat models of innate anxiety. This
anxiolytic-like effect was independent from known adverse effect of
benzodiazepine, such as memory impairment, motor coordination deficits, and
ethanol interactions. We have also demonstrated that
KNT-127 showed potent and rapid
antidepressant-like effects in rat models of depression. This
antidepressant-like effect was independent from known adverse effect of
selective serotonin reuptake inhibitor (SSRI), such as digestive symptoms. Therefore, we propose that DOP should be considered as an attractive target for the development of novel
psychotropic drugs, without producing the adverse effects associated with
benzodiazepine anxiolytics and SSRI
antidepressants. Very recently, we developed another delta agonist NC-2800 with a different structure. NC-2800 is now in the preclinical stage using the CiCLE fund supported by AMED (Japanese Agency for Medical Research and Development).